We propose to clarify the effects of fatty acids on circadian rhythms in the mold Neurospora. The study will begin with the synthesis of "knobbed" analogs of fatty acids, which will contain an alkoxy group near the middle of the alkyl chain. The knobbed analogs will be used to supplement cel strains of Neurospora, which are deficient in fatty acid synthetase, and thus grow poorly without exogenous fatty acid supplemtnes. A circadian rhythm of conidia formation is easily observed in bd mutants, and the period of this rhythm in the double mutant bd cel is dramatically lengthened by unsaturated or short-chain saturated fatty acid supplements. Unsaturated and short-chain fatty acids share a capacity to "fluidize" membranes. Since knobbed analogs should also disrupt and thereby fluidize membranes, they were chosen as a third type of possible period-perturbing supplement. The rationale for this approach is supported by theoretical connections between membrane fluidity and basic circadian rhythm mechanisms which have been made in a recent model. This model accommodates the singular fact of "temperature compensation" in circadian clock processes. Investigation of the effects of the knobbed fatty acids on the Neurospora circadian rhythm, and studies on their uptake and metabolism, should help distinguish among the various possible modes of action of period-lengthening fatty acids. The ultimate goal of these investigations is a better understanding of circadian rhythms at the molecular and cellular level, which will eventually lead to improved understandings of rhythms at higher organizational levels that directly affect human health and disease.